Function and interactions of a protein bridge between the inner membrane complex and subpellicular microtubules in .

is an intracellular parasite that utilizes peripheral membrane and cytoskeletal structures for essential functions such as host cell invasion and replication. These include the inner membrane complex (IMC) and the underlying longitudinal subpellicular microtubules (SPMT) that provide support for the IMC and give the parasite its distinctive crescent shape. Although the IMC and SPMTs have been studied separately, the mechanisms linking these adjacent structures remain largely unknown.

The interactome of the Bakers' yeast peroxiredoxin Tsa1 implicates it in redox regulation of intermediary metabolism, glycolysis, and zinc homeostasis.

Zinc (Zn) is an essential nutrient supporting a range of critical processes. In the yeast Saccharomyces cerevisiae, Zn deficiency induces a transcriptional response mediated by the Zap1 activator, which controls a regulon of ∼80 genes. A subset support Zn homeostasis by promoting Zn uptake and its distribution between compartments, while the remainder mediate an 'adaptive response' to enhance fitness of Zn-deficient (ZnD) cells.

Cytoplasmic and nuclear protein interaction networks of the synapto-nuclear messenger CRTC1 in neurons reveal cooperative chromatin binding between CREB1 and CRTC1, MEF2C and RFX3.

Glutamatergic stimulation of excitatory neurons triggers the synapto-nuclear translocation of the cAMP response element (CRE) binding protein (CREB) regulated transcription coactivator 1 (CRTC1), resulting in the transcription of CREB1 target genes. Whether and how CRTC1 and CREB1 interact with other transcription factors to regulate activity-dependent transcription, and what the role of CRTC1 is in neurons beyond the activation of CREB1 regulated transcription, remains unknown. To address these questions in an unbiased manner, we used proximity labeling to identify CRTC1-proximal proteins in cytoplasmic and nuclear compartments of rodent forebrain neurons.

SE(3)-equivariant ternary complex prediction towards target protein degradation.

Targeted protein degradation (TPD) has rapidly emerged as a powerful modality for drugging previously "undruggable" proteins. TPD employs small molecules like PROTACs and molecular glue degraders (MGD) to induce target protein degradation via the formation of a ternary complex with an E3 ligase. However, the rational design of these degraders is severely hindered by the difficulty of obtaining these ternary structures.

REM transcription factors and GDE1 shape the DNA methylation landscape through the recruitment of RNA polymerase IV transcription complexes.

In plants, the maintenance of DNA methylation is controlled by several self-reinforcing loops involving histone methylation and non-coding RNAs. However, how methylation is initially patterned at specific genomic loci is largely unknown. Here we describe four Arabidopsis REM transcription factors, VDD, VAL, REM12 and REM13, that recognize specific sequence regions and, together with the protein GENETICS DETERMINES EPIGENETICS1 (GDE1), recruit RNA polymerase IV transcription complexes.

Global Landscape of Human Kinase Motifs in Viral Proteomes.

The successful establishment of infection relies on an ability to sense and adapt to the host signaling state. One key mechanism of virus-host sensing is host-mediated post-translational modifications of viral proteins. While viral protein phosphorylation by host kinases is known to modulate viral functions, the global prevalence of kinase motifs across diverse viruses, and the signaling pathways they reflect, remains to be systematically explored.

The cell-surface shared proteome of astrocytes and neurons and the molecular foundations of their multicellular interactions.

Neurons and astrocytes are predominant brain cells that extensively interact, but the molecular basis of their interactions remains largely unexplored. We identified and mapped striatal astrocytic and neuronal cell-surface proteins (CSPs) and found that many were shared, representing the cell-surface shared proteome of astrocytes and neurons (CS SPAN) bridging striatal astrocyte-neuron interaction sites. CS SPAN was replete with extracellular matrix proteins, cell adhesion molecules, transporters, ion channels, and G protein-coupled receptors.

Structural basis for L-isoaspartyl-containing protein recognition by the PCMTD1 cullin-RING E3 ubiquitin ligase.

A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging organismal survival. While repair through methylation by PCMT1 has been previously shown to suppress L-isoaspartyl accumulation, we provide an additional mechanism for L-isoaspartyl maintenance through PCMTD1, a cullin-RING ligase (CRL).

Proteolytic processing and host nuclear targeting of the novel effector GRA84 in .

and its relative are apicomplexan pathogens that secrete an array of dense granule proteins into the parasitophorous vacuole and host cell, where they play roles in acquiring nutrients and modulating host cell functions. Here, we characterize the novel GRA protein GRA84 in and , which is secreted into the PV and exported into the host cell nucleus. Disruption of does not affect in vitro parasite replication or establishment or maintenance of the chronic infection in vivo.

TNF-Stimulated Gene-6, Part of Extracellular Vesicles in Adipose Tissue-Derived Mesenchymal Stem Cell Concentrated Conditioned Medium, Affects Microglial Activity.

Identifying the specific bioactive molecules produced by mesenchymal stem cells (MSCs) and the signaling pathways and cell types upon which they act is critical to developing MSC-based therapeutics for inflammatory diseases with high unmet needs. Our study aimed to investigate the impact of extracellular vesicle (EV)-derived TNF-Stimulated Gene-6 (TSG-6, from adipose tissue-derived mesenchymal stem cell concentrated conditioned medium, ASC-CCM or TSG-6 overexpression in ASC using ORF expression-ready clone) on microglia and its potential anti-inflammatory effects. EV but not non-vesicular secretome prepared by ultracentrifugation confirmed the expression of TSG-6 exclusively in the small EV (sEV) fraction.

Sex and Depot Specific Adipocyte Proteome Profiling In Vivo via Intracellular Proximity Labeling.

Adipose tissue has varying distributions and metabolic properties between the sexes. Inherent sex-specific differences in adipocytes may heighten the risk of metabolic disease in males. Analysis of the adipocyte proteome can potentially provide important insight.

Trypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms.

The flagellum of drives the parasite's characteristic screw-like motion and is essential for its replication, transmission, and pathogenesis. However, the molecular details of this process remain unclear. Here, we present high-resolution (up to 2.

SE(3)-Equivariant Ternary Complex Prediction Towards Target Protein Degradation.

Targeted protein degradation (TPD) induced by small molecules has emerged as a rapidly evolving modality in drug discovery, targeting proteins traditionally considered "undruggable." This strategy induces the degradation of target proteins rather than inhibiting their activity, achieving desirable therapeutic outcomes. Proteolysis-targeting chimeras (PROTACs) and molecular glue degraders (MGDs) are the primary small molecules that induce TPD.

The interactome of the Bakers' yeast peroxiredoxin Tsa1 implicates it in the redox regulation of intermediary metabolism, glycolysis and zinc homeostasis.

Zinc (Zn) is an essential nutrient supporting a range of critical processes. In the yeast , Zn deficiency induces a transcriptional response mediated by the Zap1 activator, which controls a regulon of ~80 genes. A subset support zinc homeostasis by promoting zinc uptake and its distribution between compartments, while the remainder mediate an "adaptive response" to enhance fitness of zinc deficient cells.

Mdm38/LETM1 couples ion homeostasis and proteostatic mechanisms in the inner mitochondrial membrane.

The mitochondrial inner membrane is among the most protein-dense cellular membranes. Its functional integrity is maintained through a concerted action of several conserved mechanisms that are far from clear. Here, using the baker's yeast model, we functionally characterize Mdm38/LETM1, a disease-related protein implicated in mitochondrial translation and ion homeostasis, although the molecular basis of these connections remains elusive.

Histone H3 lysine 4 methylation recruits DNA demethylases to enforce gene expression in Arabidopsis.

Patterning of DNA methylation in eukaryotic genomes is controlled by de novo methylation, maintenance mechanisms and demethylation pathways. In Arabidopsis thaliana, DNA demethylation enzymes are clearly important for shaping methylation patterns, but how they are regulated is poorly understood. Here we show that the targeting of histone H3 lysine four trimethylation (H3K4me3) with the catalytic domain of the SDG2 histone methyltransferase potently erased DNA methylation and gene silencing at FWA and also erased CG DNA methylation in many other regions of the Arabidopsis genome.

Plant BCL-DOMAIN HOMOLOG proteins play a conserved role in SWI/SNF complex stability.

The SWItch/Sucrose Non-Fermenting (SWI/SNF) complexes are evolutionarily conserved, ATP-dependent chromatin remodelers crucial for multiple nuclear functions in eukaryotes. Recently, plant BCL-DOMAIN HOMOLOG (BDH) proteins were identified as shared subunits of all plant SWI/SNF complexes, significantly impacting chromatin accessibility and various developmental processes in Arabidopsis. In this study, we performed a comprehensive characterization of mutants, revealing the role of BDH in hypocotyl cell elongation.

Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.

Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, parasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin.

CLSY docking to Pol IV requires a conserved domain critical for small RNA biogenesis and transposon silencing.

Eukaryotes must balance the need for gene transcription by RNA polymerase II (Pol II) against the danger of mutations caused by transposable element (TE) proliferation. In plants, these gene expression and TE silencing activities are divided between different RNA polymerases. Specifically, RNA polymerase IV (Pol IV), which evolved from Pol II, transcribes TEs to generate small interfering RNAs (siRNAs) that guide DNA methylation and block TE transcription by Pol II.

PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity.

Adipose tissue regulates energy homeostasis and metabolic function, but its adaptability is impaired in obesity. In this study, we investigate the impact of acute PPARγ agonist treatment in obese mice and find significant transcriptional remodeling of cells in the stromal vascular fraction (SVF). Using single-cell RNA sequencing, we profile the SVF of inguinal and epididymal adipose tissue of obese mice following rosiglitazone treatment and find an induction of ribosomal factors in both progenitor and preadipocyte populations, while expression of ribosomal factors is reduced with obesity.

MOTS-c modulates skeletal muscle function by directly binding and activating CK2.

MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems.

Plant BCL-Domain Homologues play a conserved role in SWI/SNF complex stability.

The SWItch/Sucrose Non-Fermenting (SWI/SNF) complexes are evolutionarily conserved, ATP-dependent chromatin remodelers crucial for multiple nuclear functions in eukaryotes. Recently, plant BCL-Domain Homolog (BDH) proteins were identified as shared subunits of all plant SWI/SNF complexes, significantly impacting chromatin accessibility and various developmental processes in Arabidopsis. In this study, we performed a comprehensive characterization of mutants, revealing a previously overlooked impact on hypocotyl cell elongation.